GLP1 RA use tied to increased risk of rapidly worsening retinopathy in type 2 diabetes
USA: Glucagon-like peptide-1 receptor agonists (GLP1 RA) are significantly associated with an increased risk of diabetic retinopathy (DR) with cardiovascular benefits (CV) in type 2 diabetes (T2D) patients, says a recent study published in the Journal of Diabetes and its Complications.
The risk was observed in four major clinical trials that have shown CV benefits in type 2 diabetes including, LEADER, SUSTAIN 6, PIONEER 6, and REWIND, and was also evident in subgroups of clinical trials with follow-up longer than 52 weeks, comparing GLP1 RA (liraglutide, semaglutide, and dulaglutide) with a placebo or with patients having diabetes for more than 10 years.
The effect of GLP1 RAs on diabetic retinopathy remains controversial. Misleading results could have been generated as previous reviews combined data from randomized clinical trials (RCTs) with or without cardiovascular (CV) benefits and did not address confounders. Yilin Yoshida, Tulane University School of Medicine, New Orleans, LA, United States of America, and colleagues, therefore, aimed to examine the effect of GLP1RA on DR in type 2 diabetes in RCTs with or without CV benefits and distinguish the effect by major confounders.
For this purpose, the researchers by using reference lists conducted electronic searches of multiple databases and a manual search. A total of 13 randomized controlled trials examining the effect of GLP1 RA on health outcomes/adverse events including DR or DR complications in T2DM were included. A random-effects model meta-analysis was performed.
Based on the study, the researchers reported the following findings:
- GLP1RA was associated with an elevated risk of rapidly worsening DR in four major RCTs with CV benefits in T2DM (OR 1.23).
- The association between GLP1 RA and DR was significant in subgroups of RCTs with length over 52 weeks (1.2), using placebo as a comparator (1.22).
- In subgroups with patients who had T2DM ≥10 years (1.19) or with subjects enrolled from multiple countries (1.2), the association appeared to be evident but did not reach statistical significance.
"GLP1 RA including semaglutide, liraglutide and dulaglutide are associated with an increased risk of rapidly worsening DR in RCTs with CV benefits," the researchers wrote.
"Further data from clinical studies with longer follow-up purposefully designed for DR risk assessment, particularly including patients of established DR are warranted," they concluded.
Reference:
Yoshida Y, Joshi P, Barri S, Wang J, Corder AL, O'Connell SS, Fonseca VA. Progression of retinopathy with glucagon-like peptide-1 receptor agonists with cardiovascular benefits in type 2 diabetes - A systematic review and meta-analysis. J Diabetes Complications. 2022 Jul 5:108255. doi: 10.1016/j.jdiacomp.2022.108255. Epub ahead of print. PMID: 35817678.
